Activation of transient receptor potential vanilloid 4 channels dilates rat retinal arterioles through nitric oxide- and BK_Ca channel-dependent mechanisms in vivo.

Transient receptor potential vanilloid 4 (TRPV4) channel, a cation channel expressed in nearly all cell types, plays an important role in the regulation of vascular tone. In the present study, we examined the effect of GSK1016790A, an activator of TRPV4 channels, on the diameter of retinal blood vessels in rats and the underlying mechanisms. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Intravenous infusion of GSK1016790A (0.2-2 μg kg^-1 min^-1) increased retinal arteriolar diameter in a dose-dependent manner. The higher dose of GSK1016790A (2 μg kg^-1 min^-1) slightly decreased blood pressure. These responses to GSK1016790A were significantly attenuated by intravenous injection of GSK2193874 (0.3 mg/kg), an antagonist of TRPV4 channels. Intravitreal injection of N^ω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase or iberiotoxin, an inhibitor of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel, significantly attenuated the GSK1016790A-induced increases in retinal arteriolar diameter. These results suggest that activation of TRPV4 channels dilates rat retinal arterioles through NO- and BK_Ca channel-dependent mechanisms in vivo.

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